RESUMO

We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post-symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post-symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment.

RESUMO

Since the emergence of SARS-CoV-2 in December 2019, more than 12,000 mutations in the virus have been identified. These could cause changes in viral characteristics and directly impact global public health. The emergence of variants is a great concern due to the chance of increased transmissibility and infectivity. Sequencing for surveillance and monitoring circulating strains is extremely necessary as the early identification of new variants allows public health agencies to make faster and more effective decisions to contain the spread of the virus. In the present study, we identified circulating variants in samples collected in Belo Horizonte, Brazil, and detected a recombinant lineage using the Sanger method. The identification of lineages was done through gene amplification of SARS-CoV-2 by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). By using these specific fragments, we were able to differentiate one variant of interest and five circulating variants of concern. We were also able to detect recombinants. Randomly selected samples were sequenced by either Sanger or Next Generation Sequencing (NGS). Our findings validate the effectiveness of Sanger sequencing as a powerful tool for monitoring variants. It is easy to perform and allows the analysis of a larger number of samples in countries that cannot afford NGS.

Assuntos

COVID-19 , Sequenciamento de Nucleotídeos em Larga Escala , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , COVID-19/epidemiologia , COVID-19/virologia , Brasil/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Monitoramento Epidemiológico , Recombinação Genética , Filogenia , RNA Viral/genética , Mutação

RESUMO

Introduction: SARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough to avoid the emergence of variants capable of evading immune response induced by prior infections and vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 and BQ.1.1, the antibody response of a cohort vaccinated with a two doses CoronaVac protocol and followed by two heterologous booster doses. Methods: To assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 and 18 months after CoronaVac protocol). For each time point, individuals were divided into 3 subgroups, based on the number of additional doses received (No booster, 1 booster and 2 boosters), and a viral microneutralization assay was performed to evaluate neutralization titers and seroconvertion rate. Results: The findings presented here show that, despite the first booster, at 9m time point, improved neutralization level against omicron ancestor BA.1 (133.1 to 663.3), this trend was significantly lower for BQ.1.1 and BA.5 (132.4 to 199.1, 63.2 to 100.2, respectively). However, at 18m time point, the administration of a second booster dose considerably improved the antibody neutralization, and this was observed not only against BA.1 (2361.5), but also against subvariants BQ.1.1 (726.1) and BA.5 (659.1). Additionally, our data showed that, after first booster, seroconvertion rate for BA.5 decayed over time (93.3% at 12m to 68.4% at 18m), but after the second booster, seroconvertion was completely recovered (95% at 18m). Discussion: Our study reinforces the concerns about immunity evasion of the SARS-CoV-2 omicron subvariants, where BA.5 and BQ.1.1 were less neutralized by vaccine induced antibodies than BA.1. On the other hand, the administration of a second booster significantly enhanced antibody neutralization capacity against these subvariants. It is likely that, as new SARS-CoV-2 subvariants continue to emerge, additional immunizations will be needed over time.

Assuntos

Vacina BNT162 , Vacinas contra COVID-19 , Vacinas de Produtos Inativados , Humanos , Anticorpos Antivirais , Imunização , SARS-CoV-2 , Anticorpos Neutralizantes

RESUMO

Between 2016 and 2018, Brazil experienced major sylvatic yellow fever (YF) outbreaks that caused hundreds of casualties, with Minas Gerais (MG) being the most affected state. These outbreaks provided a unique opportunity to assess the immune response triggered by the wild-type (WT) yellow fever virus (YFV) in humans. The plaque reduction neutralization test (PRNT) is currently the standard method to assess the humoral immune response to YFV by measuring neutralizing antibodies (nAbs). The present study aimed to evaluate the humoral immune response of patients from the 2017-2018 sylvatic YF outbreak in MG with different disease outcomes by using PRNTs with a WT YFV strain, isolated from the 2017-2018 outbreak, and a vaccine YFV strain. Samples from naturally infected YF patients were tested, in comparison with healthy vaccinees. Results showed that both groups presented different levels of nAb against the WT and vaccine strains, and the levels of neutralization against the strains varied homotypically and heterotypically. Results based on the geometric mean titers (GMTs) suggest that the humoral immune response after a natural infection of YFV can reach higher levels than that induced by vaccination (GMT of patients against WT YFV compared to GMT of vaccinees, P < 0.0001). These findings suggest that the humoral immune responses triggered by the vaccine and WT strains of YFV are different, possibly due to genetic and antigenic differences between these viruses. Therefore, current means of assessing the immune response in naturally infected YF individuals and immunological surveillance methods in areas with intense viral circulation may need to be updated.IMPORTANCEYellow fever is a deadly febrile disease caused by the YFV. Despite the existence of effective vaccines, this disease still represents a public health concern worldwide. Much is known about the immune response against the vaccine strains of the YFV, but recent studies have shown that it differs from that induced by WT strains. The extent of this difference and the mechanisms behind it are still unclear. Thus, studies aimed to better understand the immune response against this virus are relevant and necessary. The present study evaluated levels of neutralizing antibodies of yellow fever patients from recent outbreaks in Brazil, in comparison with healthy vaccinees, using plaque reduction neutralization tests with WT and vaccine YFV strains. Results showed that the humoral immune response in naturally infected patients was higher than that induced by vaccination, thus providing new insights into the immune response triggered against these viruses.

Assuntos

Anticorpos Neutralizantes , Anticorpos Antivirais , Surtos de Doenças , Imunidade Humoral , Vacina contra Febre Amarela , Febre Amarela , Vírus da Febre Amarela , Febre Amarela/imunologia , Febre Amarela/epidemiologia , Febre Amarela/virologia , Humanos , Brasil/epidemiologia , Vírus da Febre Amarela/imunologia , Vírus da Febre Amarela/genética , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Masculino , Vacina contra Febre Amarela/imunologia , Feminino , Adulto , Pessoa de Meia-Idade , Vacinação , Testes de Neutralização , Adulto Jovem , Idoso , Adolescente

RESUMO

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health. Objective: The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil. Methods: Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators. Results: The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed. Conclusions: The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

RESUMO

The production of biofuels to be used as bioenergy under combustion processes generates some gaseous emissions (CO, CO2, NOx, SOx, and other pollutants), affecting living organisms and requiring careful assessments. However, obtaining such information experimentally for data evaluation is costly and time-consuming and its in situ obtaining for regional biomasses (e.g., those from Northeast Brazil (NEB) is still a major challenge. This paper reports on the application of artificial neural networks (ANNs) for the prediction of the main air pollutants (CO, CO2, NO, and SO2) produced during the direct biomass combustion (N2/O2:80/20%) with the use of ultimate analysis (carbon, hydrogen, nitrogen, sulfur, and oxygen). 116 worldwide biomasses were used as input data, which is a relevant alternative to overcome the lack of experimental resources in NEB and obtain such information. Cross-validation was conducted with k-fold to optimize the ANNs and performance was analyzed with the use of statistical errors for accuracy assessments. The results showed an acceptable statistical performance for all architectures of ANNs, with 0.001-12.41% MAPE, 0.001-5.82 mg Nm-3 MAE, and 0.03-52.30 mg Nm-3 RMSE, highlighting the high precision of the emissions studied. On average, the differences between predicted and real values for CO, CO2, NO, and SO2 emissions from NEB biomasses were approximately 0.01%, 10-6%, 0.14%, and 0.05%, respectively. Pearson coefficient provided consistent results of concentration of the ultimate analysis in relation to the emissions studied and effectiveness of the test set in the developed models.

Assuntos

Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Biomassa , Dióxido de Carbono/análise , Gases/análise , Redes Neurais de Computação

RESUMO

Yellow fever (YF) presents a wide spectrum of severity, with clinical manifestations in humans ranging from febrile and self-limited to fatal cases. Although YF is an old disease for which an effective and safe vaccine exists, little is known about the viral- and host-specific mechanisms that contribute to liver pathology. Several studies have demonstrated that oxidative stress triggered by viral infections contributes to pathogenesis. We evaluated whether yellow fever virus (YFV), when infecting human hepatocytes cells, could trigger an imbalance in redox homeostasis, culminating in oxidative stress. YFV infection resulted in a significant increase in reactive oxygen species (ROS) levels from 2 to 4 days post infection (dpi). When measuring oxidative parameters at 4 dpi, YFV infection caused oxidative damage to lipids, proteins, and DNA, evidenced by an increase in lipid peroxidation/8-isoprostane, carbonyl protein, and 8-hydroxy-2'-deoxyguanosine, respectively. Furthermore, there was a significant reduction in the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), in addition to a reduction in the ratio of reduced to oxidized glutathione (GSH/GSSG), indicating a pro-oxidant environment. However, no changes were observed in the enzymatic activity of the enzyme catalase (CAT) or in the gene expression of SOD isoforms (1/2/3), CAT, or GPx. Therefore, our results show that YFV infection generates an imbalance in redox homeostasis, with the overproduction of ROS and depletion of antioxidant enzymes, which induces oxidative damage to cellular constituents. Moreover, as it has been demonstrated that oxidative stress is a conspicuous event in YFV infection, therapeutic strategies based on antioxidant biopharmaceuticals may be new targets for the treatment of YF.

Assuntos

Antioxidantes , Febre Amarela , Humanos , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vírus da Febre Amarela/metabolismo , Glutationa/metabolismo , Estresse Oxidativo , Oxirredução , Catalase/genética , Catalase/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Dissulfeto de Glutationa/metabolismo , Hepatócitos/metabolismo , Peroxidação de Lipídeos , Glutationa Peroxidase/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/metabolismo

RESUMO

The Fundão Dam breached on 5 November 2015 (the "Event"), resulting in the release of tailings, water, scoured sediment and/or soil, and other debris to downstream watercourses. Statistical analyses using historical and recent water quality measurements were conducted to assess the extent to which water quality in the Rio Doce was recovering to baseline conditions. A review of station- and/or parameter-specific water quality time series in the Rio Doce revealed two challenges: pre-Event data imbalance and seasonality. Due to the combined effects of these two factors, data gathered from Rio Doce water quality stations before the Event likely underestimated concentration ranges and limited the usefulness of common recovery assessment techniques such as times series and water quality standard exceedance analyses. These challenges were addressed by calculating quarterly and watershed-specific river-to-tributary ratios. R code was used to produce spatiotemporal time series for 44 investigated parameters that were measured both before and after the Event. The water quality recovery durations shown by the parameter- and/or region-specific river-to-tributary ratio time series indicated that (a) turbidity provides the most conservative measure for water quality recovery; (b) chemical parameters associated with the tailings, like manganese and iron recovered faster than turbidity; and (c) other investigated parameters unrelated to the tailings showed either no discernable impact or rapid recovery after the Event. The resulting parameter- and/or region-specific river-to-tributary ratio time series provided reliable and quantifiable estimates of water quality recovery durations. The water quality in the region furthest from Fundão Dam, in Espírito Santo, recovered one year after the Event, while water quality in the closest region to Fundão Dam, upstream of Risoleta Neves (Candonga) Dam, recovered 4.2 years after the Event. Integr Environ Assess Manag 2024;20:74-86. © 2023 Newfields Companies, LLC. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Assuntos

Poluentes Químicos da Água , Qualidade da Água , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Ferro/análise , Rios , Brasil

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Mucoid degeneration of the anterior cruciate ligament (ACL) is an uncommon cause of pain in the posterior region of the knee, of unknown pathophysiology and underdiagnosed. The best treatment modality is still under discussion. Resection of the lesion with partial ACL debridement has shown good results without the occurrence of instability. The authors present a case of mucoid degeneration of the ACL treated with resection of the mucoid degeneration and partial debridement of the ACL by arthroscopy.

RESUMO

Trauma is a leading cause of death, permanent disability, and health care cost worldwide. The young and economically active are the most affected population. Exsanguination due to noncompressible torso hemorrhage is one of the most frequent causes of early death, posing a significant challenge to trauma and vascular surgeons. The possibility of limb loss due to vascular injuries must also be considered. In recent decades, the approach to vascular injuries has been significantly modified. Angiotomography has become the standard method for diagnosis, endovascular techniques are currently incorporated in treatment, and damage control, such as temporary shunts, is now the preferred approach for the patients sustaining physiological derangement. Despite the importance of this topic, few papers in the Brazilian literature have offered guidelines on vascular trauma. The Brazilian Society of Angiology and Vascular Surgery has developed Projetos Diretrizes (Guideline Projects), which includes this publication on vascular trauma. Since treating trauma patients is a multidisciplinary effort, the Brazilian Trauma Society (SBAIT) was invited to participate in this project. Members of both societies reviewed the literature on vascular trauma management and together wrote these guidelines on vascular injuries of neck, thorax, abdomen, and extremities.